A strong link has been established between alcohol intake and inadequate blood pressure control in treated hypertensives. Surprisingly, this problem has gained very little attention even though it involves a good proportion of treated hypertensives. Because recent evidence argues against the generally accepted mechanism of poor compliance with therapy as the main reason, other unidentified factors should be considered. It is, therefore, the general aim of the proposed studies herein to investigate the possibility that one of these factors involves an antagonistic interaction between alcohol and antihypertensive medication. This hypothesis is supported by recent findings from our laboratory showing that ethanol-induced hypertension in rats involves sympathetic overactivity. Furthermore, others and data of our own have shown that ethanol has a pressor effect in human hypertensives, attenuates baroreflexes and possesses an alpha blocking like activity. All these hemodynamic effects are in marked contrast with those evoked by some antihypertensive medications e.g. centrally acting drugs. The fact that the recent trend in treating hypertension involves the initial(mono) therapy regimen using these drugs, especially the newer ones guanabenz and clonidine, warrants investigating this important health related interaction. The first aim of this proposal is to investigate the hypothesis that acute ethanol administration reverses the hypotensive action of centrally acting antihypertensive drugs. The second aim is to test the hypothesis that concurrent chronic alcohol intake attenuates the therapeutic effect of clonidine and guanabenz. The third aim is to investigate the potential mechanism(s) responsible for this health-related interaction with emphasis being placed on the role of the sympathetic nervous system. The experiments proposed herein are intended to test these hypotheses in conscious spontaneously hypertensive and normotensive rats chronically instrumented for hemodynamic and electrophysiological measurements. These studies are expected to provide significant new insights about the effect of ethanol consumption on the responsiveness to antihypertensive therapy, the possible mechanism(s) by which this interaction occurs and whether this interaction is specific for centrally acting antihypertensive drugs.